tbuckley/cabot-search huggingface dataset:
Internet- and mobile-based psychological interventions for sexual dysfunctions: a systematic review and meta-analysis
Authors: Anna-Carlotta Zarski, Julia Velten, Johannes Knauer, Matthias Berking, David Daniel Ebert
Journal: npj Digital Medicine (2022)

Sexual dysfunctions are highly prevalent and undertreated. Internet- and mobile-based psychological interventions (IMIs) could be a promising addition to close this treatment gap, given their accessibility, anonymity, and scalability. This systematic review and meta-analysis investigated the efficacy of IMIs for sexual dysfunctions. A comprehensive literature search was conducted in August 2021 on randomized controlled trials investigating the effects of IMIs on sexual functioning and satisfaction compared to a control condition. Twelve RCTs with 14 comparisons were reviewed with six IMIs targeting female and six IMIs targeting male sexual dysfunctions and n = 952 participants were evaluated in the meta-analysis. IMIs were significantly more effective than control conditions (k = 11 waitlist control group, k = 3 online discussion board) at post-treatment for female sexual functioning (g = 0.59, CI: 0.28-0.90, I2 = 0%) and satisfaction (g = 0.90, CI: 0.02-1.79, I2 = 82%), and male sexual functioning (g = 0.18, CI: 0.02-0.34, I2 = 0%). No significant effect was found for male sexual satisfaction (g = 0.69, CI: -0.13-1.51, I2 = 88%) with substantial heterogeneity in studies. Most studies showed high dropout, with ten studies indicating some concern of risk of bias, and two studies showing high risk of bias. The results suggest that IMIs can be an effective treatment for sexual dysfunctions, although additional high-quality research is needed. Given the limited availability of specialized treatment for sexual dysfunctions and individual preferences for discrete treatment options, IMIs seem to be a valuable addition to routine care, empowering individuals to promote their sexual health on a guided self-help basis.
MCM6 is a critical transcriptional target of YAP to promote gastric tumorigenesis and serves as a therapeutic target
Authors: Yifei Wang, Huarong Chen, Weixin Liu, Huan Yan, Yihan Zhang, Alvin H.K. Cheung, Jinglin Zhang, Bonan Chen, Li Liang, Zhaocai Zhou, Chi Chun Wong, William K.K. Wu, Michael W.Y. Chan, Alfred S.L. Cheng, Brigette B.Y. Ma, Jun Yu, Kwok Wai Lo, Ka Fai To, Wei Kang
Journal: Theranostics (2022)

Rationale: Hyperactivation of Hippo-Yes-associated protein (YAP) signaling pathway governs tumorigenesis of gastric cancer (GC). Here we reveal that minichromosome maintenance complex component 6 (MCM6) is a critical transcriptional target of YAP in GC. We aim to investigate the function, mechanism of action, and clinical implication of MCM6 in GC. Methods: The downstream targets of YAP were screened by RNA sequencing (RNA-seq) and microarray, and further validated by chromatin immunoprecipitation PCR and luciferase reporter assays. The clinical implication of MCM6 was assessed in multiple GC cohorts. Biological function of MCM6 was evaluated in vitro, in patient-derived organoids, and in vivo. RNA-seq was performed to unravel downstream signaling of MCM6. Potential MCM6 inhibitor was identified and the effect of MCM6 inhibition on GC growth was evaluated. Results: Integrative RNA sequencing and microarray analyses revealed MCM6 as a potential YAP downstream target in GC. The YAP-TEAD complex bound to the promoter of MCM6 to induce its transcription. Increased MCM6 expression was commonly observed in human GC tissues and predicted poor patients survival. MCM6 knockdown suppressed proliferation and migration of GC cells and patient-derived organoids, and attenuated xenograft growth and peritoneal metastasis in mice. Mechanistically, MCM6 activated PI3K/Akt/GSK3β signaling to support YAP-potentiated gastric tumorigenicity and metastasis. Furthermore, MCM6 deficiency sensitized GC cells to chemo- or radiotherapy by causing DNA breaks and blocking ATR/Chk1-mediated DNA damage response (DDR), leading to exacerbated cell death and tumor regression. As there are no available MCM6 inhibitors, we performed high-throughput virtual screening and identified purpureaside C as a novel MCM6 inhibitor. Purpureaside C not only suppressed GC growth but also synergized with 5-fluorouracil to induce cell death. Conclusions: Hyperactivated YAP in GC induces MCM6 transcription via binding to its promoter. YAP-MCM6 axis facilitates GC progression by inducing PI3K/Akt signaling. Targeting MCM6 suppresses GC growth and sensitizes GC cells to genotoxic agents by modulating ATR/Chk1-dependent DDR, providing a promising strategy for GC treatment.
The N<sup>6</sup>-methyladenosine-mediated lncRNA WEE2-AS1 promotes glioblastoma progression by stabilizing RPN2
Authors: Boyan Li, Rongrong Zhao, Wei Qiu, Ziwen Pan, Shulin Zhao, Yanhua Qi, Jiawei Qiu, Shouji Zhang, Qindong Guo, Yang Fan, Hao Xu, Ming Li, Gang Li, Hao Xue
Journal: Theranostics (2022)

Background: Glioblastoma (GBM) is the most common primary brain malignancy and has high aggressiveness and a poor prognosis.N6-methyladenosine (m6A) represents the most prevalent methylation modification of lncRNAs and has been shown to play important roles in the pathophysiological processes of tumors.However, the distribution and function of m6A modifications in lncRNAs in GBM tissues have not been fully revealed.Methods: The global depiction of m6A-modified lncRNA expression patterns in GBM tumor tissues was screened via m6A high-throughput sequencing.Gain-and loss-of-function assays were performed to investigate the role of WEE2-AS1 in GBM.Mass spectrometry and RNA-pulldown, RNA immunoprecipitation (RIP), luciferase reporter and coimmunoprecipitation assays were performed to explore the mechanism of m6A-mediated upregulation of WEE2-AS1 expression and the downstream mechanism promoting the malignant progression of GBM.Results: Herein, we report the differential expression profile of m6A-modified lncRNAs in human GBM tissues for the first time.WEE2-AS1 was identified as a novel m6A-modified lncRNA that promotes GBM progression and was post-transcriptionally stabilized by IGF2BP3, an m6A reader.Moreover, we confirmed that WEE2-AS1 promoted RPN2 protein stabilization by preventing CUL2-mediated RPN2 K322 ubiquitination, thereby contributing to GBM malignant progression by activating the PI3K-Akt signaling pathway.In translational medicine, we found that blocking WEE2-AS1 expression improved the therapeutic sensitivity of dasatinib, a central nervous system penetrant that is FDA-approved in GBM.Conclusions: Overall, this work highlights that WEE2-AS1 may serve as a potential prognostic biomarker and therapeutic target in GBM, the knockdown of which significantly improves the efficacy of dasatinib, providing a promising strategy for improving targeted combination therapy for GBM patients.
Methylation of the γ<i>-Catenin</i> Gene Is Associated With Poor Prognosis of Renal Cell Carcinoma
Authors: Julia E. Breault, Hiroaki Shiina, Mikio Igawa, Leopoldo A. Ribeiro-Filho, Masao Deguchi, Hideki Enokida, Shinji Urakami, Masaharu Terashima, Masayuki Nakagawa, Christopher J. Kane, Peter R. Carroll, Rajvir Dahiya
Journal: Clinical Cancer Research (2005)

Abstract Purpose: γ-Catenin is a cell adhesion protein, and its functional loss is associated with tumor invasion and metastasis. We hypothesize that (1) promoter CpG methylation regulates the expression and function of the γ-catenin gene in renal cell carcinoma (RCC) and (2) methylation of the γ-catenin gene is associated with poor prognosis of RCC. To test these hypotheses, we analyzed the CpG methylation status of the γ-catenin gene and its correlation with clinical outcome in RCC. Experimental Design: Genomic DNA and total RNA were extracted from three renal cancer cell lines (A498, Caki-1, and Caki-2) and 54 RCC tissue samples with their corresponding normal kidney tissue samples. Expression of γ-catenin gene was analyzed by reverse transcription-PCR and immunostaining. Promoter methylation was analyzed by two different methylation-specific PCR (MSP-A and MSP-B), and the results were verified by DNA sequencing. Results: The demethylating agent (5-aza-2′-deoxycytidine) increased levels of mRNA transcript of the γ-catenin gene in three renal cancer cell lines. γ-Catenin mRNA and protein expression were significantly reduced in RCC samples compared with normal kidney samples, respectively (P &amp;lt; 0.05). MSP-A and MSP-B bands were detected in 45 of 54 (83.3%) and 49 of 54 (90.7%) RCC samples, respectively. In normal kidney, weak products of MSP-A and MSP-B were detected in 5 of 54 (9.3%) and 6 of 54 (11.1%) samples, respectively. Likewise, both MSP-A and MSP-B ratios were significantly higher in RCC samples compared with normal kidney samples, respectively (P &amp;lt; 0.01). Multivariate analysis revealed that the MSP-B ratio was a powerful and independent predictor superior to nuclear grade and Robson stage with respect to survival and disease progression (P = 0.029 and 0.0071, respectively). No mutations in the NH2-terminal region of γ-catenin were found in this study. Conclusion: Expression of γ-catenin is regulated by promoter CpG methylation, and the balance between methylated and unmethylated RCC cell populations could determine its functional role. Because the conventional nuclear grade and/or staging system have some limitations to predict precise clinical outcome, this is the first report demonstrating that promoter CpG methylation of γ-catenin can be an independent and superior predictor for survival and disease progression.
A novel portable upper gastrointestinal endoscopy system with complete functions of both diagnosis and treatment
Authors: Wen-Bin Zou, Ting Zhang, Chen He, Xiao-Dong Duan, Cui Liu, Zhao-Shen Li, Zhuan Liao
Journal: Endoscopy (2022)

Gastrointestinal (GI) disease has a high incidence in clinical practice, especially in remote areas [1] and during natural disasters. However, it is difficult to perform conventional GI endoscopy outdoors as it requires a large area, hydroelectric power, and a complex cleaning and disinfection process [2]. To overcome the above limitations, we developed a novel portable upper GI endoscopy system that is capable of performing the same functions as a conventional endoscopy system and can be packed into a suitcase.
A novel approach to remove two gastric gastrointestinal stromal tumors located in the gastric fundus
Authors: Tianying Duan, Deliang Liu
Journal: Endoscopy (2022)

A 72-year-old woman presented with a 10-month history of epigastric discomfort. Esophagogastroduodenoscopy (EGD) detected two protruding lesions located at the greater curvature of the gastric fundus ([Fig. 1]). Endoscopic ultrasound showed two hypoechoic tumors arising from the muscularis propria layer ([Fig. 2]). Computed tomography (CT) scan revealed an extraluminal component of the large mass ([Fig. 3]).
Colonic intussusception due to filiform polyposis of ulcerative colitis treated by endoscopic reduction
Authors: Kosuke Ito, Satoshi Asai, Hitomi Jimbo, Kotaro Takeshita, Takumi Ichinona, Eisuke Akamine, Naoki Fujimoto
Journal: Endoscopy (2022)

A 20-year-old man with ulcerative colitis presented with epigastric pain and hematochezia. Vital signs were stable and no peritoneal irritation signs were observed. Contrast-enhanced abdominal computed tomography showed a target sign in the descending colon, and he was diagnosed with intussusception ([Fig. 1]). After consulting surgeons, we first attempted to perform colonoscopy for diagnosis and reduction. A colonoscope (CF-Q260DI; Olympus, Tokyo, Japan) was inserted under fluoroscopy ([Fig. 2]). No obvious necrotic findings were observed in the mucosa. A huge granule-aggregating mass was found in the descending colon, and intussusception due to this mass was easily reduced by endoscopic CO2 insufflation. After endoscopic reduction, we advanced the endoscope and confirmed that the mass was originally located near the hepatic flexure of the transverse colon ([Fig. 3]), and the intussusception had been completely reduced ([Video 1]). The biopsy specimen taken from the mass was revealed to be an inflammatory polyposis (filiform polyposis) [1]. On the second day, as the abdominal pain was reduced and normal bowel movement was established, the patient started taking his meals and was discharged the following day.
Successful withdrawal of migrated pancreatic stent with a prototype guiding sheath
Authors: Mako Ushio, Ko Tomishima, Shigeto Ishii, Yusuke Takasaki, Koichi Ito, Toshio Fujisawa, Hiroyuki Isayama
Journal: Endoscopy (2022)

A prototype guiding sheath (UMIDAS Inc., Yokohama, Japan) is being developed for use in various procedures in pancreaticobiliary endoscopy. The guiding sheath can approach any area in the pancreaticobiliary duct that is difficult to approach through a stricture or tortuous duct and help with the insertion of various devices.
Use of a nylon loop and transparent cap to assist in the endoscopic removal of a long and bent metal foreign body incarcerated in the duodenum
Authors: Hua Zhang, Haibo Wang, Yi Fan, Weili Hua, Biguang Tuo, Rui Xie
Journal: Endoscopy (2022)

There are many endoscope-assisted techniques that have been reported for the removal of traditional foreign bodies in the digestive tract (e. g. rat-tooth grasper, mini-snare, and end loop, among others) [1] [2] [3]. However, for any long and bent metal foreign bodies incarcerated in the duodenum or stomach, the technical difficulty is how to make the angled and sharp ends pass through the physiological narrow areas (e. g. pyloric canal, cardia, and esophageal entrance) in a relatively safe way.
Identification of a Novel Small-Molecule Inhibitor of the Hypoxia-Inducible Factor 1 Pathway
Authors: Chalet Tan, Rita G. de Noronha, Anthony J. Roecker, Beata Pyrzynska, Fatima Khwaja, Zhaobin Zhang, Huanchun Zhang, Quincy Teng, Ainsley C. Nicholson, Paraskevi Giannakakou, Wei Zhou, Jeffrey J. Olson, M. Manuela Pereira, K.C. Nicolaou, Erwin G. Van Meir
Journal: Cancer Research (2005)

Abstract Hypoxia-inducible factor 1 (HIF-1) is the central mediator of cellular responses to low oxygen and has recently become an important therapeutic target for solid tumor therapy. Inhibition of HIF-1 is expected to result in the attenuation of hypoxia-inducible genes, which are vital to many aspects of tumor biology, including adaptative responses for survival under anaerobic conditions. To identify small molecules inhibiting the HIF-1 pathway, we did a biological screen on a 10,000-membered natural product-like combinatorial library. The compounds of the library, which share a 2,2-dimethylbenzopyran structural motif, were tested for their ability to inhibit the hypoxic activation of an alkaline phosphatase reporter gene under the control of hypoxia-responsive elements in human glioma cells. This effort led to the discovery of 103D5R, a novel small-molecule inhibitor of HIF-1α. 103D5R markedly decreased HIF-1α protein levels induced by hypoxia or cobaltous ions in a dose- and time-dependent manner, whereas minimally affecting global cellular protein expression levels, including that of control proteins such as HIF-1β, IκBα, and β-actin. The inhibitory activity of 103D5R against HIF-1α was clearly shown under normoxia and hypoxia in cells derived from different cancer types, including glioma, prostate, and breast cancers. This inhibition prevented the activation of HIF-1 target genes under hypoxia such as vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1). Investigations into the molecular mechanism showed that 103D5R strongly reduced HIF-1α protein synthesis, whereas HIF-1α mRNA levels and HIF-1α degradation were not affected. 103D5R inhibited the phosphorylation of Akt, Erk1/2, and stress-activated protein kinase/c-jun-NH2-kinase, without changing the total levels of these proteins. Further studies on the mechanism of action of 103D5R will likely provide new insights into its validity/applicability for the pharmacologic targeting of HIF-1α for therapeutic purposes.
Allergen recognition by specific effector Th2 cells enables <scp>IL</scp>‐2‐dependent activation of regulatory T‐cell responses in humans
Authors: Daniel Lozano‐Ojalvo, Scott R. Tyler, Carlos J. Aranda, Julie Wang, Scott Sicherer, Hugh A. Sampson, Robert A. Wood, A. Wesley Burks, Stacie M. Jones, Donald Y. M. Leung, Maria Curotto de Lafaille, M. Cecilia Berin
Journal: Allergy (2022)

Type 2 allergen-specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen-specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance. We sought to identify regulatory components of the CD4
Liquid biopsy: current technology and clinical applications
Authors: Mina Nikanjam, Shumei Kato, Razelle Kurzrock
Journal: Journal of Hematology & Oncology (2022)

Abstract Liquid biopsies are increasingly used for cancer molecular profiling that enables a precision oncology approach. Circulating extracellular nucleic acids (cell-free DNA; cfDNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) can be isolated from the blood and other body fluids. This review will focus on current technologies and clinical applications for liquid biopsies. ctDNA/cfDNA has been isolated and analyzed using many techniques, e.g., droplet digital polymerase chain reaction, beads, emulsion, amplification, and magnetics (BEAMing), tagged-amplicon deep sequencing (TAm-Seq), cancer personalized profiling by deep sequencing (CAPP-Seq), whole genome bisulfite sequencing (WGBS-Seq), whole exome sequencing (WES), and whole genome sequencing (WGS). CTCs have been isolated using biomarker-based cell capture, and positive or negative enrichment based on biophysical and other properties. ctDNA/cfDNA and CTCs are being exploited in a variety of clinical applications: differentiating unique immune checkpoint blockade response patterns using serial samples; predicting immune checkpoint blockade response based on baseline liquid biopsy characteristics; predicting response and resistance to targeted therapy and chemotherapy as well as immunotherapy, including CAR-T cells, based on serial sampling; assessing shed DNA from multiple metastatic sites; assessing potentially actionable alterations; analyzing prognosis and tumor burden, including after surgery; interrogating difficult-to biopsy tumors; and detecting cancer at early stages. The latter can be limited by the small amounts of tumor-derived components shed into the circulation; furthermore, cfDNA assessment in all cancers can be confounded by clonal hematopoeisis of indeterminate potential, especially in the elderly. CTCs can be technically more difficult to isolate that cfDNA, but permit functional assays, as well as evaluation of CTC-derived DNA, RNA and proteins, including single-cell analysis. Blood biopsies are less invasive than tissue biopsies and hence amenable to serial collection, which can provide critical molecular information in real time. In conclusion, liquid biopsy is a powerful tool, and remarkable advances in this technology have impacted multiple aspects of precision oncology, from early diagnosis to management of refractory metastatic disease. Future research may focus on fluids beyond blood, such as ascites, effusions, urine, and cerebrospinal fluid, as well as methylation patterns and elements such as exosomes.
33528 Triple-wavelength diode laser (755 nm, 810 nm, and 1064 nm): Preliminary efficacy and safety for skin-tightening
Authors: Hwa Jung Ryu, Dong Hye Suh, Hyun Joo Kim, Snag Jun Lee, Kye Yong Song, Byeong Geun Park
Journal: Journal of the American Academy of Dermatology (2022)
Infant Leukemia
Authors: Sevgi Gözdaşoğlu
Journal: Leukemia (2022)

Infant leukemias are rare entities of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) that are generally diagnosed in infants under the age of one. Patients often present with bulky hepatosplenomegaly, leukemia cutis, central nervous system symptoms, and hyperleukocytosis. Infant leukemia has specific biological, clinical, cytologic, and cytogenetic features. Cytogenetics is an important factor for diagnosis and risk stratification. Infant B lineage ALL is characterized by a higher white blood cell count, higher incidence of KMT2A rearrangements, and negative CD10. Relapse rate is also higher in these cases. KMT2A rearrangements are clearly associated with poorer outcome in infants with ALL. KMT2A rearrangements in acute myelomonocytic leukemia (FAB M4), acute monocytic leukemia (FAB M5), and acute megakaryoblastic leukemia (FAB M7), are also common in infants, but KMT2A rearrangements are not a significant risk factor for infants with AML. As the diagnosis of megakaryoblastic leukemia is challenging, megakaryocytic markers should be investigated in all infant leukemias. It should be noted that transient abnormal myelopoiesis, a condition sharing the same morphology and immunophenotype with acute megakaryoblastic leukemia, frequently occurs in infants with Down syndrome and the somatic mutation of GATA1 is distinct in this situation.
33547 Validation of the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) scale for assessing severity of GPP
Authors: A. David Burden, Hervé Bachelez, Siew Eng Choon, Slaheddine Marrakchi, Tsen-Fang Tsai, Akimichi Morita, Mark G. Lebwohl, Milan Anadkat, Ming Tang, Christian Thoma, Kristina Callis Duffin
Journal: Journal of the American Academy of Dermatology (2022)
34321 Bimekizumab efficacy and safety through 96 weeks in patients with moderate to severe plaque psoriasis: Results from the open-label extension period of the BE RADIANT phase 3b trial
Authors: Bruce Strober, Carle Paul, Andrew Blauvelt, Diamant Thaçi, Boni Elewski, Katy White, Veerle Vanvoorden, Delphine Deherder, Fabienne Staelens, Kilian Eyerich
Journal: Journal of the American Academy of Dermatology (2022)
31028 Mutations in FLG, the gene-coding profilaggrin/filaggrin, are associated with putative hay fever in patients with atopic dermatitis
Authors: Satoko Minakawa, Yasushi Matsuzaki, Hideyuki Suwa, Michihiro Kono, Masashi Akiyama, Daisuke Dawamura
Journal: Journal of the American Academy of Dermatology (2022)
33623 Evaluation of the efficacy and tolerance of a cosmetic serum containing volcanic mineralizing water, probiotic fractions, hyaluronic acid, niacinamide, and tocopherol in patients with “face mask dermatitis”
Authors: Anne-Charlotte Kuna, Anne Guertler, Hoang Phoung Do, Elsa Devillechabrolle, Delphine Kerob, Cristel Ruini, Markus Reinholz
Journal: Journal of the American Academy of Dermatology (2022)
34660 Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, versus placebo and apremilast in moderate to severe plaque psoriasis: Achievement of absolute PASI thresholds in the phase 3 POETYK PSO-1 and PSO-2 trials
Authors: Mark Lebwohl, Melinda Gooderham, Richard B. Warren
Journal: Journal of the American Academy of Dermatology (2022)
33935 Comorbidities in rosacea, common origin or random chance?
Authors: David A. Castillo Molina, Jorge Andres Rios-Duarte, Jesus Daniel Fierro-Lozada, Sara Muñoz-Ordoñez, Maria J. Sanchez-Zapata, Jennipher Andrea Blanco-Gomez, Tatiana Solorzano-Rojas, Paula Celeste Rubiano-Mojica, Penelope A. Hirt, Diego Mauricio Martinez-Zuñiga
Journal: Journal of the American Academy of Dermatology (2022)
33325 Long-term dupilumab effectiveness on health-related quality of life (HRQoL) and work productivity in atopic dermatitis (AD): Results from RELIEVE-AD
Authors: Dimittri Delevry, Jingdong Chao, Chien-Chia Chuang, Min Yang, Brad Shumel, Bruno Martins, Gaelle Bego-Le-Bagousse, Debra Sierka, Zhixiao Wang, Bruce Strober
Journal: Journal of the American Academy of Dermatology (2022)